CBR1-IN-3 , CAS No.891101-69-2

CAS: 891101-69-2 Cat. No.: C1439288 분자식: C₁₆H₁₁ClN₂O₃ 분자량: 314.72

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

개요

CBR1-IN-3 (compound 13h) is a potent inhibitor of carbonyl reductase 1 (CBR1), with IC 50 value of 0.034 μM.

Specifications

보관 조건

Store at -20°C

배송

Ice chest + Ice pads

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이름과 식별자

분자량

314.72

Application Protocols

No item-specific, validated application protocols are provided in the Product Data for CBR1-IN-3. The following are general, literature-based procedures for small-molecule enzyme inhibitors.

• Stock preparation (general):

  • Dissolve in anhydrous DMSO to 10–50 mM, depending on solubility. Vortex, sonicate briefly, and filter if needed (0.2 µm PTFE). Aliquot and store at –20 °C.

• Biochemical CBR1 inhibition assay (general outline):

  1. Prepare assay buffer (e.g., 50 mM phosphate or HEPES, pH 7.2), add NADPH (e.g., 200 µM) and a carbonyl substrate at Km-range concentration.
  2. Pre-incubate enzyme with inhibitor (varied concentrations) for 10–15 min at room temperature.
  3. Initiate reaction with substrate or NADPH; monitor NADPH consumption at 340 nm or quantify product by LC–MS to avoid spectral interference.
  4. Determine IC50 by non-linear regression; for mechanism, measure initial rates at multiple substrate concentrations (Lineweaver–Burk or global fitting).

• Cell-based studies (general outline):

  • Dilute DMSO stocks into culture medium to achieve ≤0.1–0.5% DMSO final. Include vehicle controls. Assess cytotoxicity independently.
  • Validate target engagement with orthogonal methods (e.g., CETSA or proteomics), and confirm on-target effects with genetic controls.

• Data quality controls:

  • Include a reference CBR1 inhibitor, no-enzyme, no-substrate, and heat-inactivated controls. Evaluate detergent sensitivity to detect aggregation.

These protocols are for research use only and require optimization for each laboratory’s setup.

Biological Roles

Context for the biological target (general, literature-based):

• Carbonyl reductase 1 (CBR1) is an NADPH-dependent short-chain dehydrogenase/reductase (SDR) that catalyzes the reduction of a wide range of aromatic and aliphatic carbonyl compounds to their corresponding alcohols.
• Physiological roles include metabolism of endogenous substrates (e.g., prostaglandins, lipid peroxidation products) and xenobiotics. CBR1 participates in cellular redox balance and detoxification pathways.
• Tissue distribution: Broad expression in human tissues, with notable activity in liver and extrahepatic sites (literature, general). Subcellular localization is predominantly cytosolic.
• Cofactor dependence: Utilizes NADPH; catalytic mechanism involves a conserved Tyr-Lys-Ser triad typical of SDR enzymes.

Relevance to research use of CBR1 inhibitors (general):

• Chemical probes targeting CBR1 enable dissection of carbonyl metabolism and its impact on oxidative stress handling, eicosanoid signaling, and xenobiotic bioactivation/inactivation.
• Selectivity profiling is important due to potential cross-reactivity with related SDR/AKR family members; results should be validated using genetic controls (siRNA/CRISPR) and orthogonal assays.

Note for this product:

• No item-specific biological data (potency, selectivity, cell permeability) are provided in the Product Data for CBR1-IN-3. Users should determine functional parameters in their specific systems and consult any available CoA or technical notes supplied with the lot.

Buffer Applications

This product is not a buffering agent. However, buffer choice is critical for enzymology or cell-based assays employing CBR1-IN-3.

General assay buffer guidance (non-item-specific):

• Biochemical CBR1 activity assays: Use 50 mM potassium phosphate or HEPES buffer, pH 7.0–7.5, containing NADPH (cofactor), 0.1 mg/mL BSA, and 0.01% nonionic detergent (optional) to suppress aggregation. Include 1–5% glycerol if protein stability is an issue.
• Cell-based assays: Use physiologically relevant buffers/media (e.g., HBSS or complete culture media) with final DMSO ≤0.1–0.5% v/v. Maintain constant osmolarity and pH.
• Metal chelators: Add EDTA only if compatible with the enzyme preparation; verify that chelators do not affect CBR1 activity.

Preparation tips:

• Filter-sterilize buffers (0.22 µm) for cell assays. Degas if performing high-precision spectrophotometric or ITC experiments.
• Establish solvent controls corresponding to the highest DMSO level used. Validate that buffer components do not interfere with substrate/product detection (e.g., UV, fluorescence, or LC–MS readouts).

Item-specific information on optimal buffers, pH range, or stabilizers is not provided; determine empirically for your assay format.

Green Alternatives

Because CBR1-IN-3 is a bioactive small molecule rather than a process solvent or bulk reagent, green chemistry considerations focus on solvent choice, minimization of hazardous waste, and assay design.

Greener handling strategies (general):

• Prefer aqueous buffers with minimal DMSO (≤0.1–0.5% v/v final) for assays. Where feasible, use HEPES or phosphate buffers instead of volatile organic solvents.
• Avoid DMF and dichloromethane in routine solution prep for biological assays; reserve for analytical sample preparation when strictly necessary.
• Use microplate formats and miniaturized volumes (e.g., 384- or 1536-well plates) to reduce solvent consumption and waste.
• Consider bio-based solvents for cleaning (e.g., Cyrene, 2-MeTHF) instead of petroleum-derived solvents when compatible with the compound and downstream analysis.

Comparison of common vehicles (general)

• DMSO: High solvency; ubiquitous for stock solutions; moderate environmental impact; keep concentrations low in aqueous systems.
• Ethanol: Renewable feedstock; lower toxicity profile than many aprotic solvents; may have lower solubilizing power for heteroaromatics.
• Acetonitrile/DMF: Effective for LC–MS sample prep but less preferred in biology due to toxicity; limit volumes and ensure proper waste segregation.

Waste reduction:

• Prepare concentrated stocks to minimize freezer footprint and packaging waste; aliquot to avoid thaw–freeze cycles and disposal of degraded material.
• Adopt on-demand dilution and automated liquid handling to reduce over-preparation and assay repeats.

Pharmaceutical Uses

No pharmacopeial status, excipient role, or formulation use is provided for this item. CBR1-IN-3 is supplied strictly for research use only, as indicated in the Product Data.

General note (non-item-specific):

• Small-molecule enzyme inhibitors like CBR1-IN-3 are typically employed as research tools in discovery biology and analytical method development. They are not intended for human or veterinary use, diagnostic procedures, or clinical applications.
• If formulation studies are conducted for research purposes (e.g., permeability or stability assessments), ensure that all work is confined to non-clinical, in vitro, or ex vivo test systems and complies with institutional and regulatory guidelines.

Physical Properties

Item-specific physicochemical data are not provided in the Product Data for CBR1-IN-3.

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Purity/grade: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.
• Melting point, boiling point, density, refractive index: Not specified for this item; refer to CoA/Spec Sheet.
• Solubility: Not specified for this item; refer to CoA/Spec Sheet.

General/literature guidance for small-molecule inhibitors (non-item-specific):

• Many screening compounds are supplied as solids and are soluble in DMSO at 10–50 mM for stock preparation (literature, general). Actual solubility of CBR1-IN-3 must be verified experimentally.
• LogP, pKa, and aqueous solubility vary widely among CBR1 inhibitor chemotypes; do not assume values without the specific structure. Determine experimentally (shake-flask, potentiometric titration) if required for assay design.

Practical notes:

• If the item appears partially insoluble in DMSO, consider gentle warming (≤40 °C) and sonication. Filter through a low-protein-binding 0.2 µm PTFE membrane before biological assays to remove particulates.
• Record exact solvent, concentration, and lot information in ELN to ensure reproducibility.

Quality and Grades

• Item-specific grade/purity: Not specified for this item; refer to CoA/Spec Sheet.

Guidance on grades for small-molecule library members (general):

• Screening/Discovery grade: Typically intended for biochemical or cell-based assays; purity often ≥95% by HPLC/LC–MS (literature, general). Verify the actual purity, counterions, and residual solvent/water levels on the provided CoA.
• Analytical data package: For bioactive tools, review chromatographic purity, MS, and, if available, 1H/13C NMR to confirm identity and lot-to-lot consistency. If chirality is relevant, check enantiomeric/diastereomeric ratio data.
• Stabilizers: Not specified for this item; refer to CoA/Spec Sheet. If a stabilizer or specific counterion is used, evaluate potential assay interference and include appropriate vehicle controls.

Best practices:

• For quantitative biology, confirm identity and purity in-house (orthogonal LC–MS and NMR) prior to critical studies.
• If using in high-sensitivity assays (SPR, ITC, fluorescence), consider additional polishing (e.g., preparative HPLC) to remove trace fluorescent or aggregating impurities; document any post-purchase processing in your records.

Reaction and Applications

This product is positioned as a bioactive small molecule (CBR1 inhibitor) for research use, not as a synthetic reagent.

Research applications (general, literature-based):

• Enzyme inhibition studies: Probe the catalytic activity of human carbonyl reductase 1 (CBR1), an NADPH-dependent enzyme involved in the reduction of carbonyl substrates. Use to establish target engagement and characterize kinetic parameters (IC50, Ki, mode of inhibition) in biochemical assays.
• Pathway interrogation: Modulate carbonyl metabolism in cellular models to study roles in xenobiotic processing and endogenous prostaglandin/leukotriene pathways. Include orthogonal readouts to mitigate off-target or redox cycling artifacts.
• Chemoproteomics/target validation: When structure is available, derivatization for pull-downs or photoaffinity labels can be contemplated; confirm that modifications retain activity.

Assay design tips (non-item-specific):

• Control compounds: Include a known CBR1 inhibitor and an inactive analog to benchmark potency/selectivity.
• Aggregation/artifacts: Test with low nonionic detergent (e.g., 0.01% Triton X-100 or Tween-20) and perform dilution-to-extinction checks. Monitor for NADPH interference in spectrophotometric assays.
• Redox considerations: Some inhibitors can show assay interference through redox cycling or fluorescence. Employ orthogonal assays (LC–MS substrate/product quantification) to confirm results.

Note: No item-specific potency, selectivity, or structural information is provided; consult CoA or primary literature corresponding to CAS 891101-69-2 if available.

Reaction Conditions

Not typically applicable. CBR1-IN-3 is intended as a bioactive small-molecule inhibitor for biochemical or cell-based experimentation, not as a reagent for synthetic transformations.

General guidance (if chemical modification is attempted; literature/general):

• Solubilization: Prepare solutions in anhydrous DMSO for coupling or tagging reactions; keep water content low to preserve reagent activity.
• Conditions: Choose mild chemistries compatible with potentially sensitive heteroaromatic scaffolds (e.g., amide couplings with HATU/EDC, SuFEx, or click reactions) only after confirming the actual structure and reactive handles.
• Analytical monitoring: Use LC–MS and NMR to confirm integrity pre- and post-reaction. Check for degradation under basic or strongly oxidizing conditions.

Item-specific synthetic conditions, reactivity, or stability windows are not provided; consult structure-specific data before attempting any derivatization.

Safety and Handling

Item-specific hazard classification is not provided in the Product Data.

• GHS/CLP (item-specific):
  • Signal word: Not specified for this item; refer to SDS.
  • Hazard statements (H-codes): Not specified for this item; refer to SDS.
  • Pictograms: Not specified for this item; refer to SDS.

General laboratory safety guidance (non-item-specific):

• Handle as a research chemical of unknown toxicity. Use a fume hood or well-ventilated area.
• PPE: lab coat, safety glasses, and appropriate chemically resistant gloves (e.g., nitrile). Avoid skin contact and inhalation of dust or aerosols.
• Storage incompatibilities: Keep away from strong oxidizers and strong acids/bases until compatibility is known. Avoid prolonged exposure to moisture and light unless stability data indicate otherwise.
• First aid (overview; defer to SDS):
  • Inhalation: Move to fresh air; seek medical advice if symptoms persist.
  • Skin/eyes: Rinse with water for at least 15 minutes; remove contaminated clothing; seek medical advice if irritation continues.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.
• Spill response: Avoid dust generation. Absorb solids with inert material; collect in suitable container for disposal according to institutional and local regulations.
• Waste: Dispose as organic laboratory waste; do not release to drains. Follow your institution’s hazardous waste procedures.

Always consult the lot-specific Safety Data Sheet (SDS) for authoritative safety information.

Solvent Selection

Item-specific solubility and preferred solvents are not provided.

General guidance for small-molecule inhibitors in screening workflows (literature/general):

• Primary stock solvent: DMSO is commonly used due to broad solubilizing power and compatibility with many biochemical and cell-based assays.
• Cosolvents: If DMSO solubility is limited, mixtures such as DMSO:water (with gentle pH adjustment), or DMSO:ethanol can help. Avoid DMF/ACN in live-cell assays where possible due to cytotoxicity.
• Aqueous buffers: Use assay buffer with ≤0.1–0.5% DMSO (v/v) final concentration to minimize solvent effects on enzyme activity and cell viability; establish solvent controls matching the highest DMSO percentage used.

Selection considerations:

• Polarity: Without structural data, assume exploratory testing is needed. Prepare a solvent screening panel (DMSO, EtOH, MeOH, ACN, buffer with surfactant like 0.01% Tween-20) to evaluate solubility and avoid aggregation.
• Light/air sensitivity: If unknown, protect solutions from light (foil-wrap) and air (nitrogen headspace) during long incubations.

Comparison (general):

• DMSO vs ethanol: DMSO offers higher solubility for polar/heteroaromatic inhibitors; ethanol may reduce nonspecific effects in some cell assays but typically has lower solubilizing capacity.
• ACN/DMF: Useful for analytical sample prep; less preferred for biological assays due to toxicity; keep <0.1% final if used.

Storage and Reconstitution

Item-specific storage conditions (from Product Data):

• Store at –20 °C.
• Shipped in an ice chest with ice pads to maintain a low temperature during transit.

General handling and reconstitution (non-item-specific):

• Upon receipt: Allow the sealed container to equilibrate to room temperature before opening to prevent condensation.
• Solid material: If provided as a solid, prepare concentrated stocks in anhydrous DMSO (typical 10–50 mM). Mix thoroughly, optionally warm gently (≤40 °C) and sonicate for complete dissolution. Filter through 0.2 µm PTFE if particulates persist.
• Solution form: If supplied in solution, verify concentration and solvent on the CoA/label. Keep tightly capped; minimize headspace and repeated freeze–thaw cycles.
• Aliquoting: Dispense single-use aliquots into amber vials or plates to avoid light exposure and freeze–thaw degradation. Store at –20 °C or as otherwise indicated on the label/CoA.
• Stability: Lot-specific stability, hygroscopicity, and light sensitivity are not specified; protect from moisture and light as a precaution. Monitor for precipitation or discoloration before use.
• Thawing: Thaw on ice or at room temperature; mix gently. Avoid multiple freeze–thaw cycles; discard aliquots showing visible degradation or failing QC checks.

Research use note: For research use only. Consult the CoA and SDS for any additional, lot-specific handling guidance.

Structure and Identity

Brief description: CBR1-IN-3 is listed as a small-molecule library member annotated as an inhibitor of carbonyl reductase 1 (CBR1). Specific structural identifiers are not provided in the Product Data.

• Item-specific identifiers (from Product Data)

  • SKU: C1439288
  • Product Name: CBR1-IN-3
  • CAS: 891101-69-2
  • Molecular formula: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.
  • InChIKey: Not specified for this item; refer to CoA/Spec Sheet.

• Structural features (general/literature context)

  • “CBR1 inhibitor” nomenclature typically denotes a heteroaromatic or aryl–carbonyl–amine scaffold capable of occupying the NADPH-adjacent carbonyl-binding pocket of CBR1 (literature, general). Specific ring systems, stereochemistry, and substituents for CBR1-IN-3 are not provided.

• 2D structure description

  • Not available for this item in the provided data. Consult the Certificate of Analysis (CoA) or structure sheet if supplied with the lot.

• Notes

  • If using for computational studies (docking/SAR), obtain the exact SMILES/InChI from the CoA/specification sheet associated with the purchased lot to avoid ambiguity.

Synthetic Utility

CBR1-IN-3 is positioned as a finished small-molecule tool compound rather than a synthetic building block.

• Building-block use: Not typically applicable. No functional handles or protecting-group strategy information is available from the Product Data.
• Derivatization (general): If structural information becomes available, analog generation for SAR or biotin/photoaffinity tagging may be explored. Retain key pharmacophores necessary for CBR1 engagement and verify activity after modification.
• Reference chemistry: Without a disclosed structure, specific named reactions or cross-coupling strategies cannot be recommended. Any synthetic adaptation should be guided by the actual scaffold and literature precedents for CBR1 inhibitor chemotypes.

Conclusion: Treat this product as a bioactive probe for assays rather than as a reagent for multistep synthesis.

Target Specificity

Item-specific potency and selectivity data are not provided for CBR1-IN-3.

General considerations for CBR1 probes (literature/general):

• Primary target: Human carbonyl reductase 1 (CBR1), an SDR enzyme. Confirm activity using purified recombinant CBR1 and appropriate substrates (e.g., menadione or model aryl ketones) with NADPH.
• Off-targets to evaluate: CBR3, AKR family members (e.g., AKR1C isoforms), aldo-keto reductases, and other SDRs that share cofactor-binding motifs. Conduct selectivity panels where feasible.
• Counterscreens: Assess for redox cycling, pan-assay interference compounds (PAINS) behavior, and colloidal aggregation (detergent-sensitive inhibition, dynamic light scattering).
• Cellular specificity: Validate target engagement using genetic controls (knockdown/knockout rescue), CETSA/thermal shift, or target occupancy assays.

Note: Without item-specific data, users should generate IC50/Ki and selectivity ratios under standardized conditions and report assay formats, enzyme sources, and cofactor/substrate concentrations to enable cross-study comparison.